We propose to try to determine how influenza virus infection potentiates the pathogenic potential of Haemophilus influenzae type b (Hitb) in infant rats. The model to be studied has been developed in previous investigations and consists of intranasal (i.n.) inoculation of 10 to the 5th power TCID50 of influenza virus at age three days, followed by 10 to the 5th power cfu of Hitb i.n. at age five days and bacterial blood culture at age seven days. With this procedure, a much lower proportion of rats become bacteremic if given attenuated influenza virus or saline at age two days than occurs if given wild-type influenza virus. Most of our experiments will utilize a fully virulent, wild-type influenza virus strain. We will determine if there is accelerated growth of clones by Hitb with high polyribose phosphate (PRP) content in virus-infected nasal tissue by comparing total PRP concentration (using an ELISA assay) with the number of viable Hitb (using antiserum agar medium) in these tissues, and contrasttng virus-infected with control animals--all challenged with Hitb. We will see if infections with pneumococci and meningococci are potentiated by influenza virus in this model, and if virus-infected nasal tissues contain substances which enhance the growth of Hitb or other bacteria. We will study the possible potentiating effects of a chemical irritant (dilute HCl), and of inactivated wild-type influenza virus. We will examine respiratory tissues for histologic changes at various stages of virus infection and attempt to correlate the severity of change with degree of potentiation following i.n. inoculation of Hitb at different intervals after i.n. virus inoculation. We will also give influenza virus intraperitoneally prior to Hitb i.n., to determine if there is a systemic effect of influenza virus. We will determine the degree of potentiation of Hitb infection for other respiratory viruses (para-influenza type 2 virus, respiratory syncytial virus and coronavirus OC-43), and for additional influenza viruses shown to be attenauted for humans for volunteer studies.